Thermal Decomposition of Hydrazines from Reactive Dynamics Using the ReaxFF Reactive Force Field

We report reactive dynamics (RD) studies on: the decomposition of bulk hydrazine (N_2H_4); the decomposition of bulk monomethyl-hydrazine (CH_3N_2H_3), hereafter referred to simply as methyl-hydrazine; the decomposition of hydrazine in the presence of hydrogen peroxide (H_2O_2); and decomposition hydrazine on catalytic surfaces Pt[100] and Pt[111] under various conditions. These studies use the ReaxFF reactive force field to describe the multitude of chemical reactions in these systems for a variety of reaction conditions in order to show that this approach leads to realistic decomposition mechanisms and rates. In particular, we determined how the decomposition of hydrazine is affected by temperature, pressure, and heating rate. We analyzed chemical reaction mechanism of the decomposition of hydrazine at the studied conditions and found that at lower temperatures the initial product from hydrazine decomposition is NH_3, whereas at higher temperatures H_2 and N_2 are the dominant early products. Prominent intermediates observed during these decompositions include N_2H_3, N_2H_2, and NH_2, in agreement with quantum mechanical studies (7.3 ps at 3000 K). As the heating rate is decreased, the onset for hydrazine decomposition shifts to lower temperatures. Using a constant heating rate, we found that higher pressure (increased density) favors formation of NH_3 over N_2 and H_2. In studies of the catalytic decomposition of hydrazine on surfaces Pt[100] and Pt[111], we found that the presence of a Pt-catalyst reduces the initial decomposition temperature of hydrazine by about 50%. We found that the Pt[100]-surface is 20 times more active for hydrazine decomposition than the Pt[111]-surface, in qualitative agreement with experiments. These studies indicate how ReaxFF RD can be useful in understanding the chemical processes involved in bulk and catalytic decomposition and in oxidation of reactive species under various reaction conditions

Thermal Decomposition of Energetic Materials by ReaxFF Reactive Molecular Dynamics

We report the study of thermal decomposition of 1,3,5-trinitrohexahydro-s-triazine (RDX) bonded with polyurethane (Estane) and of the bulk hydrazine by molecular dynamics (MD) simulations equipped with the reactive force field (ReaxFF). For the polymer binder explosive, the simulation results show that the thermal decomposition of RDX is affected by the presence of the polymer binder Estane. Generally, with addition of Estane the decomposition of RDX slows down. Final products including N2, H2O, CO, CO2 and intermediates NO2, NO and HONO have been identified from the thermal decomposition processes. For the bulk hydrazine, it is found that with the increase of temperature, its decomposition increases and more N2 and H2 are generated, but NH3 molecules are consumed much faster at higher temperatures. This simulation work provides us an approach to quickly test the response of various energetic materials to thermal conditions

Overexpression of IL-1α in Skin Differentially Modulates the Immune Response to Scarification with Vaccinia Virus

Transepidermal inoculation of vaccinia virus (VV), or scarification, has been used effectively for the induction of specific and long-lasting immunity to smallpox and is superior to other routes of immunization. Scarification of individuals with atopic skin disease or immune deficiency, however, can lead to persistent viral replication and result in significant morbidity and mortality. These effects of scarification presumably reflect the unique immunological properties of skin and the immune cells resident in, or recruited to, the site of inoculation. To explore these phenomena, we utilized transgenic mice engineered to overexpress IL-1α, a critical mediator of cutaneous inflammation, in the epidermis. Following scarification with VV, both transgenic and wild-type mice develop local pox. At high doses of VV, IL-1α transgenic mice recruited immune cells to the inoculation site more rapidly and demonstrated enhanced T-cell and humoral immune responses. At limiting doses, however, IL-1α transgenic mice could effectively control virus replication without formation of pox lesions or activation of a memory response. This study suggests that IL-1 might be useful as an adjuvant to enhance antiviral immunity and promote safer vaccination strategies; however, understanding the balance of IL-1 effects on innate and adaptive immune functions will be critical to achieve optimal results

Disruption of TNFα/TNFR1 function in resident skin cells impairs host immune response against cutaneous vaccinia virus infection

One strategy adopted by vaccinia virus (VV) to evade the host immune system is to encode homologs of TNF receptors (TNFR) that block TNFα function. The response to VV skin infection under conditions of TNFα deficiency, however, has not been reported. We found that TNFR1−/− mice developed larger primary lesions, numerous satellite lesions and higher skin virus levels after VV scarification. Following their recovery, these TNFR1−/− mice were fully protected against challenge with a lethal intranasal dose of VV, suggesting these mice developed an effective memory immune response. A functional systemic immune response of TNFR1−/− mice was further demonstrated by enhanced production of VV-specific IFNγ and VV-specific CD8+ T cells in spleens and draining lymph nodes. Interestingly, bone marrow (BM) reconstitution studies using WT BM in TNFR1−/− host mice, but not TNFR1−/− BM in WT host mice, reproduced the original results seen in TNFR1−/− mice, indicating that TNFR1 deficiency in resident skin cells, rather than hematopoietic cells, accounts for the impaired cutaneous immune response. Our data suggest that lack of TNFR1 leads to a skin-specific immune deficiency and that resident skin cells play a crucial role in mediating an optimal immune defense to VV cutaneous infection via TNFα/TNFR1 signaling

Pre-existing asthma as a comorbidity does not modify cytokine responses and severity of COVID-19

Background: A significant portion of COVID-19 sufferers have asthma. The impacts of asthma on COVID-19 progression are still unclear but a modifying effect is plausible as respiratory viruses are acknowledged to be an important trigger for asthma exacerbations and a different, potentially type-2 biased, immune response might occur. In this study, we compared the blood circulating cytokine response to COVID-19 infection in patients with and without asthma. Methods: Plasma samples and clinical information were collected from 80 patients with mild (25), severe (36) or critical (19) COVID-19 and 29 healthy subjects at the John Radcliffe Hospital, Oxford, UK. The concentrations of 51 circulating proteins in the plasma samples were measured with Luminex and compared between groups. Results: Total 16 pre-existing asthma patients were found (3 in mild, 10 in severe, and 3 in critical COVID-19). The prevalence of asthma in COVID-19 severity groups did not suggest a clear correlation between asthma and COVID-19 severity. Within the same COVID-19 severity group, no differences were observed between patients with or without asthma on oxygen saturation, CRP, neutrophil counts, and length of hospital stay. The mortality in the COVID-19 patients with asthma (12.5%) was not higher than that in patients without asthma (17.2%). No significant difference was found between asthmatic and non-asthmatic in circulating cytokine response in different COVID-19 severity groups, including the cytokines strongly implicated in COVID-19 such as CXCL10, IL-6, CCL2, and IL-8. Conclusions: Pre-existing asthma was not associated with an enhanced cytokine response after COVID-19 infection, disease severity or mortality

Reactive Force Fields Based on Quantum Mechanics for Applications to Materials at Extreme Conditions

Understanding the response of energetic materials (EM) to thermal or shock loading at the atomistic level demands a highly accurate description of the reaction dynamics of multimillion-atom systems to capture the complex chemical and mechanical behavior involved: nonequilibrium energy/mass transfer, molecule excitation and decomposition under high strain/heat rates, formation of defects, plastic flow, and phase transitions. To enable such simulations, we developed the ReaxFF reactive force fields based on quantum mechanics (QM) calculations of reactants, products, high-energy intermediates and transition states, but using functional forms suitable for large-scale molecular dynamics simulations of chemical reactions under extreme conditions. The elements of ReaxFF are: - charge distributions change instantaneously as atomic coordinates change, - all valence interactions use bond orders derived uniquely from the bond distances which in turn describe uniquely the energies and forces, - three body (angle) and four body (torsion and inversion) terms are allowed but not required, - a general "van der Waals" term describes short range Pauli repulsion and long range dispersion interactions, which with Coulomb terms are included between all pairs of atoms (no bond or angle exclusions), - no environmental distinctions are made of atoms involving the same element; thus every carbon has the same parameters whether in diamond, graphite, benzene, porphyrin, allyl radical, HMX or TATP. ReaxFF uses the same functional form and parameters for reactive simulations in hydrocarbons, polymers, metal oxides, and metal alloys, allowing mixtures of all these systems into one simulation. We will present an overview of recent progress in ReaxFF developments, including the extension of ReaxFF to nitramine-based (nitromethane, HMX) and peroxide-based (TATP) explosives. To demonstrate the versatility and transferability of ReaxFF, we also present applications to silicone polymer poly-dimethylsiloxane (PDMS)

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity.

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism, and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design, and personalized medicine approaches for COVID-19